In 2018, (1) we reported that an Hsp90 co-chaperone in yeast that is not conserved in multi-cellular eukaryotes is functionally replaced by site-specific postranslational modification in human cells. Specifically, phosphorylation of the highly conserved tyrosine 627 in human Hsp90 alpha causes a long-range conformational change in the chaperone resulting in loss of dimerization of the Hsp90 N-domains. Although tyrosine 627 in yeast Hsp90 is not phosphorylated its phosphomimetic mutation has a similar effect on yeast Hsp90 conformation as does over-expression of the non-conserved yeast co-chaperone Hch1 and phosphorylation of tyrosine 627 in human Hsp90 alpha. Our data are consistent with the possibility that appearance of this posttranslational modification in higher eukaryotes represents an evolutionary substitution for Hch1 protein. (2) We showed that phosphorylation-induced unfolding of the Hsp90 co-chaperone Cdc37 promotes kinase recruitment to Hsp90 and client class-specific Hsp90 phosphorylation. During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner.